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慢性炎症性疾病生物疗法的药效学监测

Pharmacodynamic Monitoring of Biological Therapies in Chronic Inflammatory Diseases.

作者信息

Dreesen Erwin, Gils Ann

机构信息

Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, University of Leuven, Leuven, Belgium.

出版信息

Ther Drug Monit. 2019 Apr;41(2):131-141. doi: 10.1097/FTD.0000000000000571.

Abstract

BACKGROUND

Psoriasis, psoriatic arthritis, spondyloarthritis, rheumatoid arthritis, ulcerative colitis, and Crohn disease share similar underlying pathophysiological processes, providing the opportunity to treat the patients using similar biological therapies. Failure of biological treatments due to underexposure can be managed by therapeutic drug monitoring. Adjusting the treatment based on pharmacokinetic monitoring can be further improved by taking pharmacodynamic parameters such as clinical and molecular markers into account.

METHODS

Here, we critically evaluate the existing evidence, the hurdles to be taken, and the opportunities for a widespread implementation of pharmacodynamic monitoring.

RESULTS

Pharmacodynamic monitoring typically is the monitoring of biochemical markers. A pharmacodynamic marker preferably is specific for the pharmacological action of a drug, but most of the time nonspecific pharmacodynamic markers are used, such as C-reactive protein and the erythrocyte sedimentation rate. Clinical pharmacodynamic markers typically evaluate physical variables or symptoms. Although physician-reported outcomes have been studied for a longer time and often have been shown to correlate well with molecular pharmacodynamic markers and treatment outcomes, the introduction of mobile health or mHealth technologies caused a shift toward patient-reported outcomes, with the associated challenge to consistently reflect the inflammatory state, thereby preventing undertreatment or unnecessary overdosing of patients.

CONCLUSIONS

The primary goal of pharmacodynamic monitoring is to optimize the response, but it can also have an impact on safety, costs, patient adherence, etc. Ideally, the constant remote monitoring of patient-reported disease activity is expected to become the standard, facilitated by mHealth technologies.

摘要

背景

银屑病、银屑病关节炎、脊柱关节炎、类风湿关节炎、溃疡性结肠炎和克罗恩病具有相似的潜在病理生理过程,这为使用相似的生物疗法治疗患者提供了机会。因药物暴露不足导致生物治疗失败可通过治疗药物监测来处理。通过考虑临床和分子标志物等药效学参数,基于药代动力学监测调整治疗可得到进一步改善。

方法

在此,我们严格评估现有证据、需克服的障碍以及广泛实施药效学监测的机会。

结果

药效学监测通常是对生化标志物的监测。药效学标志物最好对药物的药理作用具有特异性,但大多数时候使用的是非特异性药效学标志物,如C反应蛋白和红细胞沉降率。临床药效学标志物通常评估身体变量或症状。尽管医生报告的结果已被研究较长时间,且常显示与分子药效学标志物及治疗结果有良好相关性,但移动健康或mHealth技术的引入导致向患者报告结果的转变,随之而来的挑战是始终如一地反映炎症状态,从而防止患者治疗不足或不必要的过量用药。

结论

药效学监测的主要目标是优化反应,但它也会对安全性、成本、患者依从性等产生影响。理想情况下,借助mHealth技术,对患者报告的疾病活动进行持续远程监测有望成为标准做法。

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